ALESSANDRO VANNUCCHI (FLORENCE)
RESISTANCE TO HYDROXYUREA
Center for Research and Innovation of Myeloproliferative Neoplasms, University of Florence, Italy
Hydroxyurea has been, and continues to be, a stone in the treatment of patients with
polycythemia vera and essential thrombocythemia who are considered at high risk for
thrombosis and/or are in need of cytoreduction, according to the recommendation/guidelines
of of ELN and NCCN. While most patients obtain benefits form treatment in terms of
controlling blood cell count and reducing the rate of thrombosis, a minority may not be able
to gain the required reduction in blood cell counts at optimized dose or experience side effects
at such a level to consider treatment intolerable. According to different retrospective studies,
the proportion of patients treated with HU who develop resistance and intolerance is ranked
at 11% and 13%, respectively. Criteria for defining resistance and intolerance to HU were
developed in 2010 as a consensus conference; these criteria were developed for clinical trials,
and not for being immediately transferrable to the clinical practice. Indeed, these criteria have
been used, with minor modifications, in recent clinical trial exploring the effectiveness of drug
such as JAK inhibitor ruxolitinib, finally resulting in its approval as second line drug for PV, or
ropegIFN, in patients with PV. Their use in clinical practice, on the other hand, is more
questionable in the settings of resistance when these criteria are used to judge the need to
shift therapy; for example, it may be questionable to consider in need of alternative therapy
one patients with PV who has occasional requirement of phlebotomies to control the target
hematocrit level or maintains a platelet count of 600.000/ul in an otherwise well controlled
disease and with no side effects from HU. We feel more compelling the development of severe
intolerance as recurrent ulcers or recurrent skin cancers. In these instances, careful judgement
about the opportunity to shift to second line drugs should always weight expected benefits
and expected side effects plus other opportunity considerations.
For further reading:1-6
1. Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance
to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European
LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;148(6):961-963.
2. Barbui T, Tefferi A, Vannucchi AM, et al. Philadelphia chromosome-negative classical
myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet.
Leukemia. 2018;32(5):1057-1069.
3. Guidelines N. NCCN Guidelines. Myeloproliferative neoplasms. Versione 2.2018.
2018;https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf.
4. Alvarez-Larran A, Diaz-Gonzalez A, Such E, et al. Genomic characterization of patients with
polycythemia vera developing resistance to hydroxyurea. Leukemia. 2020.
5. Alvarez-Larrán A, Kerguelen A, Hernández-Boluda JC, et al. Frequency and prognostic value of
resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. British Journal
of Haematology. 2016;172(5):786-793.
6. McMullin MF, Wilkins BS, Harrison CN. Management of polycythaemia vera: a critical review
of current data. British Journal of Haematology. 2016;172(3):337-349.
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES